ArticleGenetics in medicine : official journal of the American College of Medical Genetics2018
Genotype and phenotype correlation in von Hippel-Lindau disease based on alteration of the HIF-α binding site in VHL protein.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
- Von Hippel-Lindau disease: pathophysiological and clinical advances.Familial cancer · 2026Review
- Dysregulation of the ubiquitin-proteasome system in von Hippel-Lindau syndrome: molecular insights and clinical perspectives.Clinical and experimental medicine · 2025Review
- Cardiometabolic disease and cardio-oncology: Insights from iPSC models and tissue engineering.Cell reports. Medicine · 2025Review
- Characterization of the Pheochromocytoma-Predominant Subgroup of von Hippel-Lindau Disease.Urology · 2025Article
- Molecular dynamics reveal potential effects of novel VHL variants on VHL-Elongin C binding in ccRCC patients from Eastern India.Scientific reports · 2025Article
- Factors that predict progression of von Hippel-Lindau disease-related malignancy: a longitudinal cohort study.BMC cancer · 2025Article
- Metabolomic landscape of renal cell carcinoma in von Hippel-Lindau syndrome in a Chinese cohort.iScience · 2024Article
- Patient Sex and Origin Influence Distribution of Driver Genes and Clinical Presentation of Paraganglioma.Journal of the Endocrine Society · 2024Article
- Article
- While paradigms shift in von Hippel-Lindau management, questions remain in optimal multidisciplinary neuro-oncology care.Neuro-oncology · 2023Article
- Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies.Frontiers in pharmacology · 2023Review
- The connection between tricarboxylic acid cycle enzyme mutations and pseudohypoxic signaling in pheochromocytoma and paraganglioma.Frontiers in endocrinology · 2023Review
- Clinical and Genetic Characteristics of Retinal Capillary Hemangioblastoma in Korean Patients.Korean journal of ophthalmology : KJO · 2022Article
- Review
- Review
- Large scale genotype- and phenotype-driven machine learning in Von Hippel-Lindau disease.Human mutation · 2022Article
- Cardio-onco-metabolism: metabolic remodelling in cardiovascular disease and cancer.Nature reviews. Cardiology · 2022Review
- VHL Ser65 mutations enhance HIF2α signaling and promote epithelial-mesenchymal transition of renal cancer cells.Cell & bioscience · 2022Article
- Central Nervous System Hemangioblastoma in a Pediatric Patient Associated With Von Hippel-Lindau Disease: A Case Report and Literature Review.Frontiers in oncology · 2021Review
- Clinical diagnosis, treatment and screening of the VHL gene in three von Hippel-Lindau disease pedigrees.Experimental and therapeutic medicine · 2020Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeVon Hippel-Lindau (VHL) disease is a rare hereditary cancer syndrome that reduces life expectancy. We aimed to construct a more valuable genotype-phenotype correlation based on alterations in VHL protein (pVHL).
methodsVHL patients (n = 339) were recruited and grouped based on mutation types: HIF-α binding site missense (HM) mutations, non-HIF-α binding site missense (nHM) mutations, and truncating (TR) mutations. Age-related risks of VHL-associated tumors and patient survival were compared.
resultsMissense mutations conferred an increased risk of pheochromocytoma (HR = 1.854, p = 0.047) compared with truncating mutations. The risk of pheochromocytoma was lower in the HM group than in the nHM group (HR = 0.298, p = 0.003) but was similar between HM and TR groups (HR = 0.901, p = 0.810). Patients in the nHM group had a higher risk of pheochromocytoma (HR = 3.447, p < 0.001) and lower risks of central nervous system hemangioblastoma (CHB) (HR = 0.700, p = 0.045), renal cell carcinoma (HR = 0.610, p = 0.024), and pancreatic tumor (HR = 0.382, p < 0.001) than those in the combined HM and TR (HMTR) group. Moreover, nHM mutations were independently associated with better overall survival (HR = 0.345, p = 0.005) and CHB-specific survival (HR = 0.129, p = 0.005) than HMTR mutations.
conclusionThe modified genotype-phenotype correlation links VHL gene mutation, substrate binding site, and phenotypic diversity (penetrance and survival), and provides more accurate information for genetic counseling and pathogenesis studies.
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